Evolution by mistake

Jan 24, 2011 By Daniel Stolte

Just like erasing misspellings on a whiteboard, organisms have evolved mechanisms to deal with errors that pop up when genetic information is translated into proteins. Joanna Masel (left) and Etienne Rajon discovered that such errors help organisms adapt to evolutionary challenges. Here, they write "GATTACA" on a whiteboard, for the 1997 movie spelled with letters of the genetic alphabet. (Photo by Beatriz Verdugo/UANews)

(PhysOrg.com) -- A major driving force of evolution comes from mistakes made by cells and how organisms cope with the consequences, University of Arizona biologists have found. Their discoveries offer lessons for creating innovation in economics and society.

Charles Darwin based his groundbreaking theory of natural selection on the realization that genetic variation among organisms is the key to evolution.

Some individuals are better adapted to a given environment than others, making them more likely to survive and pass on their genes to future generations. But exactly how nature creates variation in the first place still poses somewhat of a puzzle to evolutionary biologists.

Now, Joanna Masel, associate professor in the UA's department of ecology and evolutionary biology, and postdoctoral fellow Etienne Rajon discovered the ways organisms deal with mistakes that occur while the genetic code in their cells is being interpreted greatly influences their ability to adapt to new environmental conditions  in other words, their ability to evolve.

"Evolution needs a playground in order to try things out," Masel said. "It's like in competitive business: New products and ideas have to be tested to see whether they can live up to the challenge."

The finding is reportered in a paper published in the journal Proceedings of the National Academy of Sciences.

In nature, it turns out, many new traits that, for example, enable their bearers to conquer new habitats, start out as blunders: mistakes made by cells that result in altered proteins with changed properties or functions that are new altogether, even when there is nothing wrong with the gene itself. Sometime later, one of these mistakes can get into the gene and become more permanent.

"If the mechanisms interpreting genetic information were completely flawless, organisms would stay the same all the time and be unable to adapt to new situations or changes in their environment," said Masel, who is also a member of the UA's BIO5 Institute.

Living beings face two options of handling the dangers posed by errors, Masel and Rajon wrote. One is to avoid making errors in the first place, for example by having a proofreading mechanism to spot and fix errors as they arise. The authors call this a global solution, since it is not specific to any particular mistake, but instead watches over the entire process.

The alternative is to allow errors to happen, but evolve robustness to the effects of each of them. Masel and Rajon call this strategy a local solution, because in the absence of a global proofreading mechanism, it requires an organism to be resilient to each and every mistake that pops up.

"We discovered that extremely small populations will evolve global solutions, while very large populations will evolve local solutions," Masel said. "Most realistically sized populations can go either direction but will gravitate toward one or the other. But once they do, they rarely switch, even over the course of evolutionary time."

Using what is known about yeast, a popular model organism in basic biological research, Masel and Rajon formulated a mathematical model and ran computer simulations of genetic change in populations.

Avoiding or fixing errors comes at a cost, they pointed out. If it didn't, organisms would have evolved nearly error-free accuracy in translating genetic information into proteins. Instead, there is a trade-off between the cost of keeping proteins free of errors and the risk of allowing potentially deleterious mistakes.

In previous publications, Masel's group introduced the idea of variation within a population producing "hopeful and hopeless monsters"  organisms with genetic changes whose consequences can be either mostly harmless or deadly, but rarely in between.

In the present paper, Masel and Rajon report that natural variation comes in two flavors: regular variation, which is generally bad most of the time, since the odds of a genetic mutation leading to something useful or even better are pretty slim, and what they call cryptic variation, which is less likely to be deadly, and more likely to be mostly harmless.

So how does cryptic variation work and why is it so important for understanding evolution?

By allowing for a certain amount of mistakes to occur instead of quenching them with global proofreading machinery, organisms gain the advantage of allowing for what Masel calls pre-selection: It provides an opportunity for natural selection to act on sequences even before mutations occur.

"When those proteins are bad enough, the sequences that produce them can be selected against. For example, if we imagine a protein with an altered amino acid sequence causing it to not fold correctly and pile up inside the cell, that would be very toxic to the organism."

"In this case of a misfolded protein, selection would favor mutations causing that genetic sequence to not be translated into protein or it would favor sequences in which there is a change so that even if that protein is made by accident, the altered sequence would be harmless."

"Pre-selection puts that cryptic variation in a state of readiness," Masel said. "One could think of local solutions as natural selection going on behind the scenes, weeding out variations that are going to be catastrophic, and enriching others that are only slightly bad or even harmless."

"Whatever is left after this process of pre-selection has to be better," she pointed out. "Therefore, populations relying on this strategy have a greater capability to evolve in response to new challenges. With too much proofreading, that pre-selection can't happen."

"Most populations are fairly well adapted and from an evolutionary perspective get no benefit from lots of variation. Having variation in a cryptic form gets around that because the organism doesn't pay a large cost for it, but it's still there if it needs it."

According to Masel, studying how nature creates innovation holds clues for human society as well.

"We find that biology has a clever solution. It lets lots of ideas flourish, but only in a cryptic form and even while it's cryptic, it weeds out the worst ideas. This is an extremely powerful and successful strategy. I think companies, governments, economics in general can learn a lot on how to foster innovation from understanding how biological innovation works."

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User comments : 17

"Charles Darwin based his groundbreaking theory of natural selection on the realization that genetic variation among organisms is the key to evolution."

This is incorrect. Darwin's theory was built on the physical variation within population, the observed results of agricultural selection, and biogeography (particularly island ecology. Note that it was Wallace who coined the term "ecology."

Darwin's personal ideas about the mechanism of heredity were entirely mistaken.

"Pre-selection puts that cryptic variation in a state of readiness," Masel said. "One could think of local solutions as natural selection going on behind the scenes, weeding out variations that are going to be catastrophic, and enriching others that are only slightly bad or even harmless."

What is the % of these slightly bad and notharmfull(but still not working) proteins(and the DNA coding them) compared to all proteins(and DNA coding them)?Maybe they are 0,00001%(they are too eliminate but with slower rate), I dont think these proteins has better chance to evolve to something working in the future than the ordinary proteins that are usefull right now. The all this pre-evolution is kind of some theoretical and not really practical thing.

Try to estimate does organisms living in environment which change faster have bigger rate of mutations , than the organisms which live in constant environment, and allso, does organism higher in the evolution have bigger rate of mutations, this will be interesting to be seen.

This article is confusing and this post is an attempt to go over it. I am not sure if it is the article or if the researchers are confused on the concept of using computers.

As best as I can make it out, at the moment, there is no actual evidence of this questionably defined cryptic variation. What they did was assume that something was going on and run some simulations of different populations to see what might happen IF there was such a mechanism. And they seem to think there is such a mechanism.

The mechanism SEEMS to be that proteins are not always formed correctly even if the there is no actual mutation. Which seems possible. However they said:

Sometime later, one of these mistakes can get into the gene and become more permanent.

Which is nonsense as written. Perhaps they didn't mean exactly that as it says something different later.

It provides an opportunity for natural selection to act on sequences even before mutations occur.

and

When those proteins are bad enough, the sequences that produce them can be selected against.

My guess it that they mean that gene sequences that produce sloppy proteins that can be somewhat different from one copy to the next can be selected OUT if they produce too many dangerous variants. And selected for if they produce more useful variants. Which strikes me as still being normal selection but more aimed at tuning up the gene sequence to produce a more uniform product but bent towards the better variant and away from the poor variants.

I think this makes sense within limits. They based their simulation on YEAST which I am pretty sure don't reproduce sexually and so that would not have much application to the organisms we are most interested in. US and organisms we depend on. Sexual reproduction produces TWO copies of each gene.

This allows for a LOT more change to occur in any individual or any species. One copy of a protein producing gene is often enough for survival thus allowing the other copy to mutate without killing off the individual with it.

I am thinking this research is in need of actual LAB experiments to support the simulations and it should be done with both sexual and non-sexual organisms. I say organisms rather than species because non-sexual organisms don't really fit the idea of species. They tend to have LINES of descent and not NETWORKS of relationships. Thus making them less resilient under pressure.

"I think this makes sense within limits. They based their simulation on YEAST which I am pretty sure don't reproduce sexually and so that would not have much application to the organisms we are most interested in."Actually it does reprodues sexually(strange actually the haploids are working organism, and the diploids accur only to reasemble the chromosomes- plants has undergo this proces on stage algea and moss) but it is not obligatory, and you are really rigt about the two copies of chromosomes, lots of recesive mutatons can survive in this way(yeast have only 1 copy of each it cant store errors like us).

Try to estimate does organisms living in environment which change faster have bigger rate of mutations

Yes. At least they should since every organism I can think of have chemicals that should increase mutation rates that are produced when under stress such as occurs in changing environments. I first ran across that in 2001 on the Comport Forum by a guy using the handle 'byff'. This was before I saw the idea anywhere else and he seems to have come up with it himself.

Well my point is rather different, it is logical when you have stress that the mechanism repairing DNA wont work properly=more mutation.But actually i wonder about the mechanism repairing DNA and how properly it works, it seems if it is not that good more mutations you have, but this costs lots of deaths too(lets say 99,99% are deadly or will diminish the fitness of the organism or the species), so there must be compromisable rate of errors to occur, and i wonder does this rate is different, it should be I think because different organism change with different speed, well here the environment plays roll too, but still.

So if there is a rate of error that occurss in a given point in the reproduction cycle, does that imply that the parent organism had less error/mutation? So if we could keep going back through the generations of the organism, it gets better and better? So then mutation is a loss of DNA information, not an increase? Where did this more pure organism come from in the first place?Where did the highly complicated information contained in the DNA come from? Random chance?Hmmm, interesting.

You dont take in to the account the NATURAL SELECTION....all people having problems with understanding evolution is due mainly to this thing, when a error(change in the dna that is not beneficial) occur, the organism having it is less likely to reproduce, thats it, if the mutation is beneficial it spread trough the population really fast, actually everything is math, how fast it will spread depends on how this new mutation increase the chance of survival/reproduction!Thats why organisms dont go downword but upword in their development, if you create a computer model based on this thing you will get the exact same conclusion(if you are so uncapable to get this- I dont say beleave because ther is nothing to beleave in it, it is a fact!)

No. The parents may have had the same number of mutations from their parents.

So if we could keep going back through the generations of the organism, it gets better and better?

That is Creationist thinking. It ignores selection. See Kevin for an example of that sort of Active Ignorance TM.

So then mutation is a loss of DNA information, not an increase?

Depends on the mutation BUT mutations are pretty much random and therefor do not increase information. Usually a decrease in information would result in death so there can't be many of those that allow the organism to function.

Where did this more pure organism come from in the first place?

Creationists say a god, which god depends on the religion.

Where did the highly complicated information contained in the DNA come from?

From the environment via selection. Only changes the are neutral or an improvement are likely to be retained.